P11.01.A BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QUALITY OF LIFE AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY
Authors: C F K Lorimer, S Mills, A Chalmers, I Coombes, G Thompson, J Glendenning, J Brock
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND GBM incidence peaks in the 7th and 8th decades, with median life expectancy of 3-6 months. Treatment decisions finely balance benefit to side-effects and worsening quality of life (QoL). Short-course partial brain radiotherapy, +/- chemotherapy, extends survival compared to supportive care but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. We aimed to consider putative MRI markers of brain resilience and their relationship to change in QoL amongst older patients being treated for GBM with cranial radiotherapy. MATERIAL AND METHODS BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for: relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)), contralateral medial temporal lobe volume, number and volume of T1 white matter hypointensities, and Fazekas' scale of white matter change. Radiotherapy treatment volumes were obtained from planning software. RESULTS 126 patients were enrolled from 12 UK centres; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. 56 participants completed all MRI sequences and QoL data points. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p=0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p=0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p&amp;lt;0.001). CONCLUSION This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS. Due to frailty, there was a significant attrition rate in data return. 29% of participants were too unwell by 8 weeks post treatment to attend hospital, also predicted by baseline imaging. These results promote and enable discussion of individualised treatment options with older patients with GBM, differentiating those who are likely to suffer reduced QoL and short survival rather than benefit from radiotherapy